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PurposeTo assess the efficacy of a treat-and-extend strategy with intravitreal ranibizumab for radiation-related macular edema.MethodsForty eyes with radiation-induced macular edema and decreased visual acuity were enrolled in the phase IIb, prospective clinical trial and randomized into 3 cohorts: (A) monthly ranibizumab, (B) monthly ranibizumab with targeted retinal photocoagulation (TRP), or (C) as-needed ranibizumab and TRP. In year 2, all subjects entered a treat-and-extend protocol for ranibizumab. The primary outcome measure was mean change in early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA) from baseline.ResultsThrough year 1, the mean change in ETDRS BCVA was significantly different between the three cohorts (p < 0.001); cohort A saw the largest gain with + 4.0 letters. Significant anatomic improvements were also seen in all cohorts. Comparatively, through year 2, cohorts A, B, and C had a mean change in ETDRS BCVA of − 1.9, − 3.9, and + 1.3 letters, respectively; additionally, no significant differences were found in absolute ETDRS BCVA across time (ANOVA, p = 0.123). Overall, 90% of eyes maintained VA 20/200 or better and 33.3% of subjects gained at least one line of vision. There were no significant differences in mean central macular thickness for any cohort compared to baseline (p = 0.09). The presence of retinal hemorrhage and intraretinal exudates stayed consistent from year 1 to year 2 for all cohorts.ConclusionsAmong eyes with radiation-related macular edema, a treat-and-extend regimen with ranibizumab may not result in as many visual and anatomic improvements as monthly injections. However, treat-and-extend still may prevent serious visual complications compared to historical controls. Trial registrationClinicalTrials.gov Identifier: NCT02222610

The environmental sources of microbial aerosols and processes by which they are emitted into the atmosphere are not well characterized. In this study we analyzed microbial cells and biological ice nucleating particles (INPs) in smoke emitted from eight prescribed wildland fires in North Florida. When compared to air sampled prior to ignition, samples of the air–smoke mixtures contained fivefold higher concentrations of microbial cells (6.7 ± 1.3 × 10 4  cells m −3 ) and biological INPs (2.4 ± 0.91 × 10 3  INPs m −3 active at temperatures ≥ −15 °C), and these data significantly positively correlated with PM 10 . Various bacteria could be cultured from the smoke samples, and the nearest neighbors of many of the isolates are plant epi- and endophytes, suggesting vegetation was a source. Controlled laboratory combustion experiments indicated that smoke emitted from dead vegetation contained significantly higher numbers of cells, INPs, and culturable bacteria relative to the green shrubs tested. Microbial viability of smoke aerosols based on formazan production and epifluorescent microscopy revealed no significant difference in the viable fraction (~80%) when compared to samples of ambient air. From these data, we estimate each fire aerosolized an average of 7 ± 4 × 10 9 cells and 2 ± 1 × 10 8 biological INPs per m 2 burned and conclude that emissions from wildland fire are sources of viable microbial aerosols to the atmosphere.

The spiny mouse ( Acomys ) is gaining popularity as a research organism due to its phenomenal regenerative capabilities. Acomys recovers from injuries to several organs without fibrosis. For example, Acomys heals full thickness skin injuries with rapid re-epithelialization of the wound and regeneration of hair follicles, sebaceous glands, erector pili muscles, adipocytes, and dermis without scarring. Understanding mechanisms of Acomys regeneration may uncover potential therapeutics for wound healing in humans. However, access to Acomys colonies is limited and primary fibroblasts can only be maintained in culture for a limited time. To address these obstacles, we generated immortalized Acomys dermal fibroblast cell lines using two methods: transfection with the SV40 large T antigen and spontaneous immortalization. The two cell lines (AcoSV40 and AcoSI-1) maintained the morphological and functional characteristics of primary Acomys fibroblasts, including maintenance of key fibroblast markers and ECM deposition. The availability of these cells will lower the barrier to working with Acomys as a model research organism, increasing the pace at which new discoveries to promote regeneration in humans can be made.

Objective Using participant responses from 525 different‐sex married and cohabiting African American couples, we examined the dyadic association between relational sanctification and relational forgiveness. Background Religion has a central role in the lives of many African Americans because it traditionally has been a place of refuge against stressors that disproportionally impact African Americans. However, little is known about how African American couples utilize relational sanctification as a strength. Method Data were collected from African American couples between October 2019 and January 2020 as part of a larger study called the Strong African American Couples Project. Utilizing dyadic panels from Qualtrics, this project specifically targeted African American couples who were cohabiting (n = 233) or married (n = 292) thus, enabling us to analyze a multigroup actor–partner interdependence model. Results Significant actor effects were found between sanctification and individual as well as perceived partner forgiveness in married and cohabiting couple relationships. No significant partner effects were found. Conclusion These findings highlight the importance of recognizing various aspects of religiosity and spirituality within relationships, especially for African American couples with historically high rates of dissolution and self‐rated religiosity. Implications As interventionalists work with religious and spiritual African American couples, they need to understand the role that sanctity may have within these partner relationships and the positive impact it can have on relational outcomes.

Scarcity of iron and manganese limits the efficiency of the biological carbon pump over large areas of the Southern Ocean. The importance of hydrothermal vents as a source of these micronutrients to the euphotic zone of the Southern Ocean is debated. Here we present full depth profiles of dissolved and total dissolvable trace metals in the remote eastern Pacific sector of the Southern Ocean (55–60° S, 89.1° W), providing evidence of enrichment of iron and manganese at depths of 2000–4000 m. These enhanced micronutrient concentrations were co-located with 3 He enrichment, an indicator of hydrothermal fluid originating from ocean ridges. Modelled water trajectories revealed the understudied South East Pacific Rise and the Pacific Antarctic Ridge as likely source regions. Additionally, the trajectories demonstrate pathways for these Southern Ocean hydrothermal ridge-derived trace metals to reach the Southern Ocean surface mixed layer within two decades, potentially supporting a regular supply of micronutrients to fuel Southern Ocean primary production.

The devastating bat fungal disease, white-nose syndrome (WNS), does not appear to affect all species equally. To experimentally determine susceptibility differences between species, we exposed hibernating naïve little brown myotis (Myotis lucifugus) and big brown bats (Eptesicus fuscus) to the fungus that causes WNS, Pseudogymnoascus destructans (Pd). After hibernating under identical conditions, Pd lesions were significantly more prevalent and more severe in little brown myotis. This species difference in pathology correlates with susceptibility to WNS in the wild and suggests that survival is related to different host physiological responses. We observed another fungal infection, associated with neutrophilic inflammation, that was equally present in all bats. This suggests that both species are capable of generating a response to cold tolerant fungi and that Pd may have evolved mechanisms for evading host responses that are effective in at least some bat species. These host–pathogen interactions are likely mediated not just by host physiological responses, but also by host behavior. Pd-exposed big brown bats, the less affected species, spent more time in torpor than did control animals, while little brown myotis did not exhibit this change. This differential thermoregulatory response to Pd infection by big brown bat hosts may allow for a more effective (or less pathological) immune response to tissue invasion.

BackgroundEarly assessment of patients with suspected transient ischaemic attack (TIA) is crucial to provision of effective care, including initiation of preventive therapies and identification of stroke mimics. Many patients with TIA present to emergency medical services (EMS) but may not require hospitalisation. Paramedics could identify and refer patients with low-risk TIA, without conveyance to the ED. Safety and effectiveness of this model is unknown.AimTo assess the feasibility of undertaking a fully powered randomised controlled trial (RCT) to evaluate clinical and cost-effectiveness of paramedic referral of patients who call EMS with low-risk TIA to TIA clinic, avoiding transfer to ED.MethodsThe Transient Ischaemic attack Emergency Referral (TIER) intervention was developed through a survey of UK ambulance services, a scoping review of evidence of prehospital care of TIA and convening a specialist clinical panel to agree its final form. Paramedics in South Wales, UK, were randomly allocated to trial intervention (TIA clinic referral) or control (usual care) arms, with patients’ allocation determined by that of attending paramedics.Predetermined progression criteria considered: proportion of patients referred to TIA clinic, data retrieval, patient satisfaction and potential cost-effectiveness.ResultsFrom December 2016 to September 2017, eighty-nine paramedics recruited 53 patients (36 intervention; 17 control); 48 patients (31 intervention; 17 control) consented to follow-up via routine data. Three intervention patients, of seven deemed eligible, were referred to TIA clinic by paramedics. Contraindications recorded for the other intervention arm patients were: Face/Arms/Speech/Time positive (n=13); ABCD2 score >3 (n=5); already anticoagulated (n=2); crescendo TIA (n=1); other (n=8). Routinely collected electronic health records, used to report further healthcare contacts, were obtained for all consenting patients. Patient-reported satisfaction with care was higher in the intervention arm (mean 4.8/5) than the control arm (mean 4.2/5). Health economic analysis suggests an intervention arm quality-adjusted life-year loss of 0.0094 (95% CI −0.0371, 0.0183), p=0.475.ConclusionThe TIER feasibility study did not meet its progression criteria, largely due to low patient identification and referral rates. A fully powered RCT in this setting is not recommended.Trial registration number ISRCTN85516498.

Background: The Canadian Nosocomial Infection Surveillance Program (CNISP) observed increased mortality among neonatal intensive care unit (NICU) patients with central-line–associated bloodstream infection (CLABSI) starting in 2017. In this study, we compared NICU patients with CLABSIs before and after 2017, and quantified the impact of epidemiological factors on 30-day survival. Methods: We included 1,276 NICU patients from 8–16 participating CNISP hospitals from the pre-2017 period (2009–2016) and the post-2017 period (2017–2022) using standardized definitions and questionnaires. We used Cox regression modeling to assess the impact of age at date of positive culture, sex, birthweight, CLABSI microorganism, region of the country, and surveillance period (before 2017 vs after 2017) on time to 30-day all-cause mortality from date of positive culture. Gestational age was not available for this analysis. We reported model outputs as hazard ratios with 95% CIs. Results: In total, 769 (60%) NICU CLABSIs were reported in the pre-2017 period and 507 (40%) in the post-2017 period. The 30-day all-cause mortality rate was 8% (n = 100 of 1,276) overall, and significantly higher after 2017 (12%, n = 61 of 507) than before 2017 (5%, n = 39 of 769) ( P < .001). During the post-2017 period, cases were significantly younger: 16 days (IQR, 9–33) versus 21 days (IQR, 11–49) ( P = .002). Median days from ICU admission to infection were shorter: 14 (IQR, 8–31) versus 19 (IQR, 10–41) ( P < .001). More gram-negative CLABSIs were identified (29% vs 24%; P = .040) and fewer gram-positive CLABSIs were identified (64% vs 72%; P = .006) compared to the pre-2017 period. Mortality was higher in CLABSIs caused by gram-negative bacteria (15%, n = 50 of 328) than gram-positive bacteria (4.4%, n = 39 of 877) ( P < .001), and mortality was higher in neonates with birthweight <1,000 g (11%, n = 71 of 673) compared to those weighing ≥1,000 g (5%, n = 28 of 560) ( P < .001). Adjusting for all other factors, survival modeling indicated that NICU CLABSIs identified in the post-2017 period had 2.12 (95% CI, 1.23–3.66) times the hazard ratio of 30-day all-cause mortality compared to those before 2017 ( P < .006). Those identified with a gram-positive bacterium had a 0.28 hazard ratio (95% CI, 0.12–0.65) of 30-day mortality compared to those with a gram-negative bacterium or fungus ( P = .003). In the fully adjusted model, age, sex, and birthweight were not significantly associated with NICU CLABSI survival. Conclusions: NICU patients with CLABSIs had significantly higher all-cause mortality between 2017–2022 compared to 2009–2016, and those who acquired gram-positive–associated CLABSIs had improved survival compared to other organisms. Further work is needed to identify and understand factors driving the increased mortality among NICU CLABSI patients from 2017–2022. Disclosures: None

INTRODUCTION:Transient Ischaemic Attack (TIA) is a neurologic event with symptom resolution within 24 hours. Early specialist assessment of TIA reduces risk of stroke and death. National United Kingdom (UK) guidelines recommend patients with TIA are seen in specialist clinics within 24 hours (high risk) or seven days (low risk).We aimed to develop a complex intervention for patients with low risk TIA presenting to the emergency ambulance service. The intervention is being tested in the TIER feasibility trial, in line with Medical Research Council (MRC) guidance on staged development and evaluation of complex interventions.METHODS:We conducted three interrelated activities to produce the TIER intervention:*. Survey of UK Ambulance Services (n = 13) to gather information about TIA pathways already in use*. Scoping review of literature describing prehospital care of patients with TIA*. Synthesis of data and definition of intervention by specialist panel of: paramedics; Emergency Department (ED) and stroke consultants; service users; ambulance service managers.RESULTS:The panel used results to define the TIER intervention, to include:1.. Protocol for paramedics to assess patients presenting with TIA and identify and refer low risk patients for prompt (< 7day) specialist review at TIA clinic2.. Patient Group Directive and information pack to allow paramedic administration of aspirin to patients left at home with referral to TIA clinic3.. Referral process via ambulance control room4.. Training package for paramedics5.. Agreement with TIA clinic service provider including rapid review of referred patientsCONCLUSIONS:We followed MRC guidance to develop a clinical intervention for assessment and referral of low risk TIA patients attended by emergency ambulance paramedic. We are testing feasibility of implementing and evaluating this intervention in the TIER feasibility trial which may lead to fully powered multicentre randomized controlled trial (RCT) if predefined progression criteria are met.

INTRODUCTION:Patients who experience Transient Ischaemic Attack (TIA) should be assessed and treated in a specialist clinic to reduce risk of further TIA or stroke. But referrals are often delayed. We aimed to identify published studies describing pathways for emergency assessment and referral of patients with suspected TIA at first medical contact: primary care; ambulance services; and emergency department.METHODS:We conducted a scoping literature review. We searched four databases (PubMed, CINAHL, Web of Science, Scopus). We screened studies for eligibility. We extracted and analysed data to describe setting, assessment and referral processes reported in primary research on referral of suspected TIA patients directly to specialist outpatient services.RESULTS:We identified eight studies in nine papers from five countries: 1/9 randomized trial; 6/9 before-and-after designs; 2/9 descriptive account. Five pathways were used by family doctors and three by Emergency Department (ED) physicians. None were used by paramedics. Clinicians identified TIA patients using a checklist incorporating the ABCD2 tool to describe risk of further stroke, online decision support tool or clinical judgement. They referred to a specialist clinic, either directly or via a telephone helpline. Anti-platelet medication was often given, usually aspirin unless contraindicated. Some patients underwent neurological and blood tests before referral and discharge. Five studies reported reduced incident of stroke at 90 days, from 6-10 percent predicted rate to 1.2-2.1 percent actual rate. Between 44 percent and 83 percent of suspected TIA cases in these studies were directly referred to stroke clinics through the pathways.CONCLUSIONS:Research literature has focused on assessment and referral by family doctors and ED physicians to reduce hospitalization of TIA patients. No pathways for paramedic use were reported. Since many suspected TIA patients present to ambulance services, effective pre-hospital assessment and referral pathways are needed. We will use review results to develop a paramedic referral pathway to test in a feasibility trial.